Moms Taking Valproate While Pregnant Increase Risk of Autism

Dec. 1, 2008 -- Women who take the epilepsy drug valproate while pregnant may increase their child's risk of autism, a new study shows.

British researchers looked at 632 children, almost half of whom were exposed to epilepsy drugs during gestation. Nine of the 632 have been diagnosed with autism, and one has shown symptoms of the disorder, Rebecca Bromley, a PhD student and one of the researchers at the University of Liverpool, tells WebMD.

Sixty-four of the children were exposed to valproate during pregnancy, 44 were exposed to lamotrigine, 76 to carbamazepine, 14 to other single-medication therapies, and 51 to polytherapy treatments for the neurological disorder.

The study, published in the journal Neurology, showed that seven of the children with autism had mothers who took epilepsy drugs while pregnant, including four who were exposed to valproate and a fifth who was exposed to valproate and lamotrigine.

The children whose mothers were taking valproate alone for epilepsy were seven times more likely to develop autism, compared to children whose mothers did not have epilepsy and were not taking any drug while pregnant, the study shows.
Counseling Prior to Pregnancy

The risk seen with valproate was not seen with the other epilepsy drugs, Bromley says. None of the children in the study had any known family history of autism.

"The take-home message is that women with epilepsy should be provided with counseling regarding their condition and its treatment prior to pregnancy," Bromley tells WebMD in an email interview. "It is important to consider that not every child is affected."

She says women with epilepsy should not stop taking their current epilepsy treatments without medical consultation with their doctors.

Bromley says three youngsters born to women without epilepsy who were not medicated also were diagnosed with autism.

That's the same rate as reported in the general population, Bromley says. The autistic children were tested at the ages of 1, 3, and 6. Two-thirds of the children were 6 years old by the time the study ended.

"The children were diagnosed independently of our study team by community psychiatrists with normal clinical practice," Bromley tells WebMD.

"This study highlights the importance of pre-conceptual advice, information, and treatment for women with epilepsy from her physician," Bromley says. "Parents who have concerns regarding the development of their child should consult their family doctor."

She says women who are pregnant and require medical treatment should talk to their doctors about possible effects on unborn babies.
Effects on Brain Development

Page Pennell, MD, director of the epilepsy program at Emory University in Atlanta, says the study is "very helpful" because it "is confirmatory of other smaller studies that we need to be concerned about, not only the effects of the medications during the first trimester, but also about continued effects of the medication on the developing brain."

Previous studies suggested concern about the effects of valproate in particular, Pennell tells WebMD, and that "the effects may be more selective for verbal abilities. The strength of this study that stands out is, there was really a rather large cohort of patients followed prior to birth and then in a systematic way up to the age of 6 years old."

Sodium valproate is an effective drug used to control seizures, Bromley says. She adds that some women have been prescribed the medication because "it is very effective at controlling the type of epilepsy they have."

Pennell says the study suggests the need to "consider exposure throughout the entire pregnancy" and even before conception. "Also, this study raises concern not only for the effects on brain development in general, but the specific finding of autism spectrum disorders points out that the children should be followed closely to be able to identify features of autism during development to allow early intervention."

She says she'd recommend that women of childbearing age steer clear of valproate unless it's the only medication that can control seizures. "Most of these women unfortunately have to be on a medicine. But the idea is, women of childbearing age should be on another anti-epileptic drug."

Pennell says 50% percent of pregnancies in the U.S. are unplanned, so women of childbearing age should talk carefully with their doctors about any anti-epileptic medications.

Laureen Cassidy, a vice president for Abbott Laboratories, which manufactures Depakote, a brand-name version of valproate, says "uncontrolled seizures can cause permanent damage" to the brains of children and "for pregnant women can be fatal to both mother and child." The product's label "makes it clear that it should not be used as a first-line treatment for women of childbearing age."

Raquel Powers, another spokeswoman, says "it's a global drug" and that its risks are well known.